Triple Quadrupole Mass Spectrometer Detector Research Articles

Routine oxygen heterocyclic compounds analysis of fragrances using an eco-friendly liquid chromatography coupled to tandem mass spectrometry method

ABSTRACT Coumarin and furocoumarins characterization in cosmetics plays an important role in protecting consumer health. The analytical technique mostly employed for the analysis of these molecules is certainly liquid chromatography coupled to photodiode array or mass spectrometer detectors. The aim of this article was to investigate on the oxygen heterocyclic compounds content in fifty hydro alcoholic fragrances using a fast, sensitive and eco-friendly liquid chromatography coupled to a triple quadrupole mass spectrometer detector analytical method without any sample pre-treatment. To the best of the author’s knowledge, this is the first research article on the quantification of thirty-six oxygen heterocyclic compounds in hydro alcoholic fragrances in less than 4 min and with the use of water/ethanol as mobile phase. Thanks to the good performance of the analytical method used, this can be proposed among the routine methods for the quality control of cosmetics and finished products.

Macrocystis pyrifera: A Potential Source of Bioactive Compounds

Background: The Mexican brown seaweed Macrocystis pyrifera is currently unexploited. While this seaweed harvested in other regions has been characterized, changes in the composition can be observed, making it relevant to have a better understanding of the Mexican variety. Objective: The objective of this study was to perform a characterization of the Mexican seaweed M. pyrifera in terms of phenolic and carotenoid profiles, mineral content, antioxidant activity, and chemical composition. Methods: Chemical composition, mineral content, total phenolic content (TPC), and antioxidant activity (ORAC) were measured. Also, the phenolic compounds and carotenoids were quantified using an HPLC coupled with a triple quadrupole mass spectrometer detector. Results: Carbohydrates (48.81 ± 0.05%) were the most abundant macronutrient, while lipids represented only 0.23 ± 0.01 % of the total. From the analyzed minerals (Na, Ca, P, K, and Mg), K was the most abundant with 15,545.23 ± 23.72 mg/100 g. To quantify the phenolic compounds, TPC, and ORAC, two extracts were used (water, and methanol: water (90:10 v/v)), for the carotenoid profile only the latter was used. The most abundant phenolic compound was phloroglucinol (4.45 ± 0.21 μg/g). Ten carotenoids were identified, fucoxanthin the most abundant (1,124.93 ± 3.4 μg/g). Finally, while there was no significant difference (p > 0.05) in the TPC, with values ranging between 16.07 and 17.01 mg GAE/ g, the methanol: water (90:10 (v/v)) extract presented a significantly higher (p < 0.05) antioxidant activity. Conclusion: The characterization of this seaweed can help to determine its potential for several applications.

Extraction of anabolic steroids with aqueous-organic mixtures from hexanic solutions

The extraction of anabolic steroids (1,4-androstadiene-3,17-dione; 17α-methyltestosterone; 19-norethiocholanolone; 4-hydroxytestosterone; 4-androstene-3,17-dione; 5α-androstane-3β,17β-diol; dehydroepiandrosterone; calusterone; clostebol; methandienone; methyldienolone; nandrolone; testosterone; epitestosterone; tibolone; 19-norandrostenedione; 1-methylene-5α-androstan-3α-ol-17-one) by aqueous-organic mixtures from hexane solutions was studied at the temperature (20 ± 1) °C. Based on the experimental data obtained, the partition ratios of anabolic steroids were calculated, which were used to optimise the standard sample preparation procedure in the process of determining the compounds under study in biologically active dietary supplements and specialised sports nutrition. It was found that the most effective and selective extractants from hydrocarbon solutions are water-acetonitrile mixtures containing from 10 to 20 % by volume of water. An extraction technique has been developed for sample preparation of biologically active dietary supplements for subsequent gas chromatographic determination of anabolic steroids in them using a triple quadrupole mass spectrometric detector. The proposed method is characterised by a standard deviation of 10–15 % and a detection limit about 10 μg/kg of biologically active dietary supplements, which makes it possible to reliably determine impurities of prohibited anabolic steroids in them.

A new functional food ingredient enriched by Phytoecdisteroids and Polyphenols from quinoa grains (Chenopodium quinoa Willd.)

Objective: Quinoa grains (Chenopodium quinoa Willd.) contain a large number of secondary metabolites. Phytoecdysteroids and polyphenols, secondary metabolites, are of great interest for research today. The aim of the study is a method development for the extraction of biologically active substances (BAS) from quinoa grains to obtain a functional food ingredient (FFI) enriched with phytoecdysteroids and polyphenols. Materials and methods: The content of phytoecdysteroids at each stage of quinoa extract production was determined by two methods: HPLC with a spectrophotometric detector and HPLC with a mass spectrometer. The content of total polyphenols was determined by the Folin-Ciocalteu method. The flavonoid profile was determined using a liquid chromatography system with a diode array spectrophotometric detector and a triple quadrupole mass spectrometric detector. Results: The chosen technological scheme for the production of FFI can concentrate more than 200 times the major phytoecdysteroid 20-hydroxyecdysone major in quinoa in the final product relative to the raw material. The maximum yield of flavonoids in the final product was observed in cases of 20 and 40% ethanol extraction. Conclusion: These results lead to the conclusion that highly enriched sources of BAS can be obtained using fairly simple technological approaches and commercially available reagents from quinoa grains.

HPLC method for simultaneous determination of impurities and degradation products in Cardiazol

Aim. The aim of study was to develop a simple and accurate procedure that could be applied for the determination of impurities and degradation products in cardiazol. Materials and methods. Separation in samples was carried out with Acquity H-class UPLC system (Waters, Milford, USA) equipped with Acquity UPLC BEH C18 column (2.1 × 50 mm, 1.7 μm) (Waters, Milford, USA). Xevo TQD triple quadrupole mass spectrometer detector (Waters Millford, USA) was used to obtain MS/MS data. Mobile phase A: 0.1% solution of trifluoroacetic acid R in water R; Mobile phase B: acetonitrile R. Samples were chromatographed in gradient mode (Table 1). Flow rate of the mobile phase: 1 ml / min. Column temperature: 30 °С. Detection: at 240 nm wavelength. Injection volume: 10 μl. Results. The retention time of the main substance is about 18.5 minutes. The order of the peak, the retention times and relative retention times: impurity B (12.04, 0.65); impurity А (18.5; 0.98); Cardiazol (18.87; 1.00). The LOD and LOQ values obtained were in the range of 30 ng/mL to 100 ng/mL and 80 ng/mL to 310 ng/mL respectively (with respect to sample concentration of 2 mg/ml). Linearity was established in the range of LOQ level to 0.2% having regression coefficients in the range of 0.9996 to 0.9999. The change in the temperature of the column affects the degree of separation of cardiazol and the impurity A, and thus, with a decrease of 5 ° C, the degree of separation is (1.06), while with increasing this index (3.43). When changing the flow rate of the mobile phase, the degree of separation changes in the following order, with a decrease to 0.9 ml / min separation (1.90), with an increase in speed to 1.1 ml / min (2.45). When the number of mobile phase B decreases by 5%, the degree of separation varies by (2.65), with an increase of 5% (1.82). In comparison with the chromatogram of the tested solution, the substance is not resistant to the action of peroxide, alkaline and acid decomposition. Conclusion. 1) HPLC method was developed and validated for the simultaneous detection and quantitation of impurities formed during the synthesis of cardiazol. 2) The method proved to be sensitive, selective, precise, linear, accurate and stability-indicating.

A novel accurate LC-MS/MS method for quantitative determination of Z-lumirubin

Although phototherapy (PT) is a standard treatment for neonatal jaundice, no validated clinical methods for determination of bilirubin phototherapy products are available. Thus, the aim of our study was to establish a such method for clinical use. To achieve this aim, a LC-MS/MS assay for simultaneous determination of Z-lumirubin (LR) and unconjugated bilirubin (UCB) was conducted. LR was purified after irradiation of UCB at 460 nm. The assay was tested on human sera from PT-treated neonates. Samples were separated on a HPLC system with a triple quadrupole mass spectrometer detector. The instrument response was linear up to 5.8 and 23.4 mg/dL for LR and UCB, respectively, with submicromolar limits of detection and validity parameters relevant for use in clinical medicine. Exposure of newborns to PT raised serum LR concentrations three-fold (p < 0.01), but the absolute concentrations were low (0.37 ± 0.16 mg/dL), despite a dramatic decrease of serum UCB concentrations (13.6 ± 2.2 vs. 10.3 ± 3.3 mg/dL, p < 0.01). A LC-MS/MS method for the simultaneous determination of LR and UCB in human serum was established and validated for clinical use. This method should help to monitor neonates on PT, as well as to improve our understanding of both the kinetics and biology of bilirubin phototherapy products.

African baobab (Adansonia digitata) fruit as promising source of procyanidins

Baobab is an endemic African plant rich in health-promoting compounds and still not extensively studied. Characterization of bioactive molecules in baobab fruit by means of LC system coupled with a photodiode array and a triple quadrupole mass spectrometer detector is here reported. This work provides a qualitative and quantitative profile of polyphenols in baobab pulp, shell, kernel and seeds. Baobab pulp is a rich source of ascorbic acid, (−)-epicatechin and procyanidin B2 (135.6, 104.8, and 100.1 mg/100 g). Moreover, a HPLC preparative method to isolate procyanidin fraction from pulp was developed, revealing how the antioxidant activity of baobab pulp not only depend on the ascorbic acid content but also on the presence of procyanidins. The use of baobab fruit pulp as promising healthy food or food supplement is also discussed.

Organic Aerosol Characterization and Source Identification in Karachi, Pakistan

With its rapidly growing population and large industrial base, the megacity of Karachi, Pakistan, has been subjected to an increasing amount of ambient particulate matter (PM). Fine particulate matter (PM2.5) in Karachi was collected every 24 hours from January 8 to January 29, 2006. The samples were extracted and analyzed by gas chromatography-mass spectrometry (GC-MS) and ultra-performance liquid chromatography (UPLC) coupled with a triple quadrupole mass spectrometric detector (TQD) and time-of-flight (TOF) mass spectrometer. The daily PM2.5 levels ranged from 99.5 to 251.1 µg m–3 with a mean of 177.4 µg m–3, averaging 4–10-fold higher than the WHO guideline for 24-hour averaged PM2.5 (25 µg m–3). We found that the day-of-the-week variations of PM2.5 demonstrate Sundays have significantly lower concentrations (with a t-based confidence level of 95%), indicating that weekly behavioral patterns affect local PM2.5 concentrations. A significant negative correlation was found between the daily concentrations of levoglucosan, a biomass burning tracer, and the average daily temperatures (r = –0.589, p = 0.004), implicating heating as a major source of biomass burning emissions. Results indicate that polyaromatic hydrocarbons, hopanes, steranes, and alkanes are mainly emitted from fossil fuels and the combustion of carbonaceous materials. Organosulfates (OSs) and sulfonates were also quantified; significant correlations between OSs and sulfonates indicate a common source and/or similar formation mechanisms, while correlations with hopanes, steranes, and levoglucosan suggest their emission from primary sources such as fossil fuels and biomass burning. Qualitative analysis suggests the presence of a C6–C9 alkyl sulfate series. Through this study, the chemical composition and origin of the organic fraction of PM2.5 in Karachi has been evaluated for the first time, and the results indicate a strong anthropogenic influence on combustion emissions, particularly those from biomass and fossil fuel burning.

C18 core-shell column with in-series absorbance and fluorescence detection for simultaneous monitoring of changes in stilbenoid and proanthocyanidin concentrations during grape cane storage

Grape canes, the residues from the annual pruning of vines, contain high levels of inducible (E)-resveratrol and also oligomeric stilbenoids and proanthocyanidins. These two families of phenolic compounds are bioactive, but to quantify them in a single chromatographic run using only ultraviolet detection is a difficult task. To overcome this limitation, a chromatographic method was developed using a core shell column for separation, an ultraviolet-visible diode array detector (DAD) and a fluorescence (FL) detector connected in series for quantification, with an electrospray ionization interface (ESI) and a triple quadrupole mass spectrometric detector (MS/MS) added for identification of the analytes. The proanthocyanidins (+)-catechin, (−)-epicatechin, procyanidins B1, B2, and C1, an unknown dimer and trimer, two prodelphinidin dimers, and monogallate procyanidin dimers were detected in the tested grape cane samples. The stilbenoids detected were (E)-resveratrol, (E)-piceatannol, (E)-piceid, (E)-ε-viniferin, vitisin B, a glycosylated monomer, three oxidized dimers, an unknown dimer and a tetramer, pallidol, hopeaphenol, (E)-δ-viniferin, and (E)-ω-viniferin. However, this method required 60min for each analysis. A faster and more efficient method for quantitative analysis was developed based on HPLC-DAD-FL, reducing the time required to 24min for the simultaneous quantification of proanthocyanidins and stilbenoids in Cabernet Sauvignon, Pinot Noir, and Tintorera grape canes stored at controlled temperatures and relativity humidities for 134days after pruning. To the best of our knowledge, this is the first time a prodelphinidin dimer has been quantified in grape canes. The incorporation of fluorescence detection in series with DAD not only allowed the quantification of proanthocyanidins, it also improved the detectability of some minor stilbenoids present in the canes, such as (E)-piceid. The (E)-resveratrol and (E)-piceatannol levels increased significantly during cane storage, while those of (E)-ε-viniferin and ampelopsin A did not show significant increases. The relative humidity had a determining effect on the levels of (E)-resveratrol and (E)-piceatannol in the canes of all varieties studied; their concentrations were higher at a relative humidity of 60% than at 70%. This is the first time that the proanthocyanidin profiles of canes stored after pruning were monitored under controlled conditions of temperature, time and relative humidity. The concentration of (−)-epicatechin decreased during storage under both relative humidities. Furthermore, the levels of proanthocyanidin B1 and the prodelphinidin dimer also decreased to a certain extent.

ВИЗНАЧЕННЯ РИСПЕРИДОНУ В БІОЛОГІЧНОМУ МАТЕРІАЛІ МЕТОДОМ УЛЬТРАЕФЕКТИВНОЇ РІДИННОЇ ХРОМАТОГРАФІЇ

Запропоновано умови ідентифікації та кількісного визначення рисперидону методом ультраефективної рідинної хроматографії з тандемною мас-спектрометрією на колонці BEH C18 в зразках біологічного матеріалу. Витяжки отримували шляхом настоювання гомогенізованих проб печінки та мозку з водою, підкисленою оксалатною кислотою. Кислі витяжки очищали методом флеш-хроматографії на колонках GraceResoIv ™ SiIica 5g / 25mI (Grace, USA). Як елюент використано 0,5 % розчин аміаку в 96 % етанолі.

Determination of trimethylamine, trimethylamine N-oxide, and taurine in human plasma and urine by UHPLC-MS/MS technique.

Trimethylamine-N-oxide (TMAO) is produced in the liver from trimethylamine (TMA) and is an important cellular osmolyte and potential atherogenic factor. Taurine is involved in cholesterol metabolism and also serves as a cellular osmolyte. Given their significant biological functions, the development of reliable measurement techniques is crucial to further study their role in health and disease METHODS: A new ultrahigh performance liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous determination of TMA, TMAO, and taurine in plasma and urine. The method consisted of a deproteinization step using methanol/acetonitrile (15:85) that contained 0.2% formic acid and isotope-labeled internal standards. Samples were separated by centrifugation and injected into the UHPLC system. Quantification was conducted using a triple-quadrupole mass spectrometer detector with electrospray ionization interface in positive mode. The limits of detection ranged from 0.08 to 0.12μmol/L. The calibration curves were linear (r≥0.999) over the range examined (0.15-400μmol/L) for all compounds. The inter- and intra-day coefficients of variations were≤14.5% for TMA and ≤8% for TMAO and taurine. TMAO and taurine were found to be stable in EDTA plasma for at least 14 months at -70°C. Mean recoveries ranged from 95% to 109% and the relative matrix effects were≤4.0%. The method was applied to study physiological and pre-analytical factors in plasma and urine samples. The new UHPLC-MS/MS method has good accuracy, precision, and recovery. The assay combines simple sample processing with a short run time, making it well suited for high-throughput routine clinical or research purposes.

Automated screening of reversed-phase stationary phases for small-molecule separations using liquid chromatography with mass spectrometry.

There are various reversed-phase stationary phases that offer significant differences in selectivity and retention. To investigate different reversed-phase stationary phases (aqueous stable C18 , biphenyl, pentafluorophenyl propyl, and polar-embedded alkyl) in an automated fashion, commercial software and associated hardware for mobile phase and column selection were used in conjunction with liquid chromatography and a triple quadrupole mass spectrometer detector. A model analyte mixture was prepared using a combination of standards from varying classes of analytes (including drugs, drugs of abuse, amino acids, nicotine, and nicotine-like compounds). Chromatographic results revealed diverse variations in selectivity and peak shape. Differences in the elution order of analytes on the polar-embedded alkyl phase for several analytes showed distinct selectivity differences compared to the aqueous C18 phase. The electron-rich pentafluorophenyl propyl phase showed unique selectivity toward protonated amines. The biphenyl phase provided further changes in selectivity relative to C18 with a methanolic phase, but it behaved very similarly to a C18 when an acetonitrile-based mobile phase was evaluated. This study shows the value of rapid column screening as an alternative to excessive mobile phase variation to obtain suitable chromatographic settings for analyte separation.

Analysis of 17 neurotransmitters, metabolites and precursors in zebrafish through the life cycle using ultrahigh performance liquid chromatography-tandem mass spectrometry.

An ultrahigh performance liquid chromatography-tandem mass spectrometry method for the identification and quantification of neurotransmitters, metabolites and precursors at different stages in zebrafish life was developed. Betaine, glutamine, glutamic acid, γ-aminobutyric acid, phosphocholine, glycerophosphocholine, cytidine 5'-diphosphocholine, choline, acetylcholine, dopamine, norepinephrine, serotonin, tyrosine, epinephrine, tryptophan, 5-hydroxyindolacetic acid and agmatine were selected as analytes. The method consisted of a simple deproteinization of samples using methanol and formic acid, subsequent injection onto the chromatographic equipment and quantification with a triple quadrupole mass spectrometer detector using an electrospray ionization interface in positive mode. Limits of detection ranged from 0.02 to 11ngmL(-1) and limits of quantification from 0.1 to 38ngmL(-1), depending on the analyte. The method was validated according to US Food and Drugs Administration (FDA) guideline for bioanalytical assays. Precision, expressed as relative standard deviation (%RSD), was lower than 15% in all cases, and the determination coefficient (R(2)) was equal or higher than 99.0% with a residual deviation for each calibration point lower than ±25%. Mean recoveries were between 85% and 115%. The method was applied to determine of these compounds in zebrafish from early stages of development to adulthood and showed the time-course of neurotransmitters and others neurocompounds through the life cycle. The possibility of measuring up to 17 compounds related with the main neurotransmitter systems in a simple analytical method will complement and reinforce the use of zebrafish in multiple applications in the field of neurosciences. The proposed method will facilitate future studies related with brain development.

Quantitative determination of neurotransmitters, metabolites and derivates in microdialysates by UHPLC–tandem mass spectrometry

The main objective of the present work is to study the time-course of rat brain neurotransmitters in vivo after an oral challenge with a nutritional ingredient or an external stimulus, such as a chemical agent. An ultrahigh performance liquid chromatography–tandem mass spectrometry method for the identification and quantification of neurotransmitters, metabolites and derivates in microdialysates from rat brain was previously developed. Betaine, glutamine, glutamic acid, gamma-aminobutyric acid, phosphocholine, glycerophosphocholine, cytidine 5'-diphosphocholine, choline, acetylcholine, dopamine, norepinephrine, serotonin, tyrosine, epinephrine, tryptophan and 5-hydroxyindoleacetic acid were selected as analytes. The method involves direct injection of samples of microdialysates from rat brain onto the chromatographic equipment and quantification with a triple quadrupole mass spectrometer detector using an electrospray ionization interface in positive mode. The limits of detection ranged from 0.1 to 50ngmL−1 and the limits of quantification from 0.3 to 200ngmL−1. The inter- and intra-day variability were lower than 15%. Recovery rates ranged from 85% to 115%.

Emerging Fusarium mycotoxins in organic and conventional pasta collected in Spain

One of the main sources of emerging Fusarium mycotoxins in human nutrition is the cereals and cereal products. In this study, an analytical method to determine enniatins A, A1, B and B1 (ENs), beauvericin (BEA) and fusaproliferin (FUS) based on Ultra-Turrax extraction followed by liquid chromatography coupled to triple quadrupole mass spectrometer detector (MS/MS QqQ), was applied for the analysis of pasta. For this purpose, 114 commercial samples of pasta were acquired from supermarkets located in Valencia. The results showed higher frequencies of contamination in organic pasta than in conventional pasta, while the concentration levels were variable for both types of pasta. In positive samples, BEA levels varied from 0.10 to 20.96μg/kg and FUS levels varied from 0.05 to 8.02μg/kg. ENs levels ranged from 0.25 to 979.56μg/kg, though the majority of the values were below 25μg/kg. Besides, it was observed the simultaneous presence of two or more mycotoxins in a high percentage of the samples. Finally, an evaluation of the dietary exposure of the emerging Fusarium mycotoxins was performed in the Spanish population. The prevalence of ENs, BEA and FUS in cereal products suggests that the toxins may pose a health risk to Spanish population.

Validation of an HPLC-MS-MS Method for the Determination of Urinary S-Benzylmercapturic Acid and S-Phenylmercapturic Acid

A high-performance liquid chromatography-tandem mass spectrometric (HPLC-MS-MS) method is presented and evaluated for the determination of S-benzylmercapturic acid (S-BMA) and S-phenylmercapturic acid (S-PMA) in human urine. Both of these compounds are important for occupational health owing to their use as biomarkers of exposure to toluene and benzene, respectively. Toluene is used extensively as a solvent, and the health hazards of benzene have been well established. The optimized urine sample preparation scheme consists of solid-phase extraction (SPE) followed by an acetone wash. The chromatographic analysis consists of a reversed-phase gradient system, which uses electrospray ionization in negative-ion mode with a triple-quadrupole mass spectrometric detector. Accuracy and precision of this method are demonstrated by a series of recovery studies of spiked human urine and synthetic urine substitute. Spike levels at 1, 2, 6, 8, and 30 ng/mL for both analytes demonstrate average recoveries (accuracy) ranging from 99 to 110%. Precision as measured by the relative standard deviation (%RSD) of multiple samples (n=9) at each concentration level was 5.3% or less for both analytes in urine. The limit of detection (LOD) is approximately 0.2 ng/mL for S-BMA and S-PMA. This data, other figures of merit and other factors, such as ion suppression of the electrospray ionization source, are discussed.

Determination of anethole trithione in human plasma using high performance liquid chromatography coupled with tandem mass spectrometric detection

A rapid, sensitive and reliable high performance liquid chromatographic method coupled with tandem mass spectrometry via electrospray ionization (ESI) source (HPLC–MS/MS) has been developed and validated for the determination of anethole trithione (ATT) in human plasma. Diazepam was employed as the internal standard (IS). Sample extracts following liquid–liquid extraction were injected into the HPLC–MS/MS system. The analyte and IS were eluted isocratically on a C 18 column, with a mobile phase consisting of methanol and aqueous ammonium acetate solution (5 mM) (80:20, v/v) .The ions were detected by a triple quadrupole mass spectrometric detector in the positive mode. Quantification was performed using selected reaction monitoring (SRM) of the transitions m/ z 240.88 → 197.91 and m/ z 285.01 → 193.02 for ATT and for the IS, respectively. The analysis time for each run was 5.0 min. The calibration curve fitted well over the concentration range of 0.02–5 ng mL −1, with the regression equation y = 1.1014 x + 0.0003631, r = 0.9992. The intra-batch and inter-batch R.S.D.% were less than 15% at all concentration levels within the calibration range. The recoveries were more than 80%. The present method provides a modern, rapid and robust procedure for the pharmacokinetic study of ATT. Some important pharmacokinetic parameters of ATT in healthy Chinese volunteers are also given for the first time.

Determination of cilnidipine, a new calcium antagonist, in human plasma using high performance liquid chromatography with tandem mass spectrometric detection

A rapid, sensitive and reliable high performance liquid chromatographic method coupled with tandem mass spectrometry (HPLC–MS/MS) has been developed and validated for the determination of cilnidipine, a relatively new calcium antagonist, in human plasma. The reversed-phase chromatographic system was interfaced with a TurboIonSpray (TIS) source. Nimodipine was employed as the internal standard (IS). Sample extracts following protein precipitation were injected into the HPLC–MS/MS system. The analyte and IS were eluted isocratically on a C18 column, with a mobile phase consisting of CH 3OH and NH 4Ac (96:4, v/v). The ions were detected by a triple quadrupole mass spectrometric detector in the negative mode. Quantification was performed using multiple reaction monitoring (MRM) of the transitions m/ z 491.2 → 122.1 and m/ z 417.1 → 122.1 for cilnidipine and for the IS, respectively. The analysis time for each run was 3.0 min. The calibration curve fitted well over the concentration range of 0.1–10 ng mL −1, with the regression equation Y = (0.103 ± 0.002) X + (0.014 ± 0.003) ( n = 5), r = 0.9994. The intra-day and inter-day R.S.D.% were less than 12.51% at all concentration levels within the calibration range. The recoveries were between 92.71% and 97.64%. The long-term stability and freeze-thaw stability were satisfying at each level. The present method provides a modern, rapid and robust tool for pharmacokinetic studies of cilnidipine.

Selective serotonin reuptake inhibitors in sewage influents and effluents from Tromsø, Norway

An analytical method for quantification of the selective serotonin reuptake inhibitors (SSRIs) citalopram, sertraline, paroxetine, fluoxetine and fluvoxamine in sewage influents and effluents from selected sewage treatment plants (STPs) has been developed and validated. This quantification method is based on solid phase extraction of 2.5 L samples, followed by liquid–liquid extraction for further sample clean up in order to minimize matrix effects during subsequent quantification. The samples were analysed on a high performance liquid chromatograph coupled to a triple quadrupole mass spectrometric detector using 0.1% ammonia in acetonitrile/water as mobile phase, with positive electrospray ionisation and multiple reaction monitoring for detection and quantification. 1-[3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)propyl]-pyrrolidine (N-7084) was used as internal standard for quantification. The recovery rates of the SSRIs ranged between 54 and 84%, and the method limit of quantification (MLQ) was between 120 and 290 pg/L for the target compounds. Samples were collected in July 2005 from three different STPs and a pump station in Tromsø, Northern Norway. Two of the STPs serve the University hospital and its psychiatric department, respectively, in addition to domestic sewage. SSRIs were detected in all samples collected. The concentrations varied greatly from below the MLQ to several hundreds ng/L. Concentrations in influents were higher compared to filtered effluents, indicating that SSRIs adsorb to particulate matter, are degraded by microorganisms, or degraded in other ways during the filtration process. However, more samples should be analysed before general conclusions can be drawn.

High-performance liquid chromatography–atmospheric pressure chemical ionization/tandem mass spectrometry for the determination of a thiol compound in plasma

A sensitive, reliable high-performance liquid chromatography (HPLC) coupled with tandem mass spectrometry (MS/MS) method was developed for the determination of a sulfhydryl-containing compound in mouse, rat, dog, monkey and human plasma samples in support of pharmacokinetic (PK) studies. The reversed-phase chromatographic system was interfaced with an atmospheric pressure chemical ionization (APCI) source. Methyl acrylate (MA) was employed to react with the sulfhydryl group of the analyte to form a derivative that was stable in dog, monkey and human plasma at room temperature. Phenylmethylsulfonyl fluoride (PMSF), a potent inhibitor of hydrolase, was used to stabilize the test thiol-MA compound in plasma samples. Sample extracts following protein precipitation were injected into HPLC–MS/MS system. The derivatized compound was detected by a triple quadrupole mass spectrometric detector in the positive ion multiple-reaction monitoring mode. The calibration curve was linear from 2.5 to 5000 ng/ml. This paper reports the development of a HPLC–APCI/MS/MS method for the quantitative determination of a thiol component in dog plasma after derivatization with methyl acrylate derivative. The procedure was used to quantitate plasma levels following oral administration of the thiol compound to beagle dogs.